Giant multilocular prostatic cystadenoma

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1 Nakamura et al. World Journal of Surgical Oncology (2019) 17:42 CASE REPORT Open Access Giant multilocular prostatic cystadenoma Yuya Nakamura 1, Dai Shida 1*, Takahiro Shibayama 4, Akihiko Yoshida 4, Yoshiyuki Matsui 2, Yasuo Shinoda 2, Shintaro Iwata 3 and Yukihide Kanemitsu 1 Abstract Background: The giant multilocular prostatic cystadenoma is a very rare benign tumor of the prostate gland. It is composed of predominantly cystic enlarged prostatic glands in a fibrous stroma and spreads extensively into the pelvis. Because of the large size at the time of diagnosis, it is not always possible to determine the exact point of origin for these multilocular cystic neoplasms. Thus, diagnosis before histological examination of a surgical specimen is often difficult. Here, we present a case involving one of the largest giant multilocular prostatic cystadenomas reported in the literature and discuss preoperative diagnoses and appropriate surgical approaches for this rare retroperitoneal tumor. Case presentation: A 50-year-old man presented with a 2-year history of abdominal distension and lower urinary. Enhanced CT showed a large retroperitoneal with multiple septations in the pelvis and lower abdomen, measuring 30 cm in size, surrounding the rectum and displacing the bladder, prostate, and seminal vesicle to the right anterior side. MRI showed multiple cysts with a simple appearance on T2-weighted images and enhanced solid components on gadolinium-enhanced fat-saturated T1-weighted images, suggesting the retroperitoneal as leiomyoma with cystic degeneration or perivascular epithelioid cell tumor. Biopsy of the showed a spindle cell tumor with focal smooth muscle differentiation. Differential diagnosis comprising leiomyoma, low-grade leiomyosarcoma, and perivascular epithelioid cell tumor was made. Complete resection of the tumor with low anterior resection of the rectum was performed. The tumor was solid with multilocular cavities containing blackish-brown and measured cm. Histologically, the tumor was composed of variously sized dilated glandular structures lined by prostatic epithelia surrounded by fibromuscular stroma. The prostatic nature of the lesions was confirmed by immunohistochemical staining of the epithelium for prostate-specific antigen. Thus, pathological diagnosis was a giant multilocular prostatic cystadenoma. Conclusions: We present our experiences with one of the largest giant multilocular prostatic cystadenomas. When a retroperitoneal huge lesion with locular cavities fills the pelvis in a male patient, the possibility of giant multilocular prostatic cystadenoma should be considered before planning for retroperitoneal tumor treatment. Keywords: Giant multilocular prostatic cystadenoma, Retroperitoneal tumor, Prostatic tumor Background Retroperitoneal tumors often present diagnostic and therapeutic challenges. Although computed tomography (CT) and magnetic resonance imaging (MRI) may be useful for diagnosis and understanding the extent of disease, a definitive diagnosis can be established only by histopathologic analysis after surgery. Knowledge of the tumor characteristics may help to narrow down the differential diagnosis. Here, we report a case of a giant multilocular prostatic cystadenoma, an extremely rare * Correspondence: dshida-tky@umin.ac.jp 1 Department of Colorectal Surgery, National Cancer Center Hospital, Tsukiji, Chuo-ku, Tokyo , Japan Full list of author information is available at the end of the article benign neoplasm that originates in the prostate glands. Fewer than 30 cases have been reported thus far [1 21]. Our case was one of the largest reported to date, as it measured 33 cm in length and occupied the whole pelvis up to the level of the navel. Case presentation A 50-year-old man presented with a 2-year history of abdominal distension. He also had lower urinary such as the sensation of incomplete voiding and increased frequency. He had no of bowel obstruction. Physical examination revealed a palpable occupying The Author(s) Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

2 Nakamura et al. World Journal of Surgical Oncology (2019) 17:42 Page 2 of 9 the lower abdomen up to the level of the navel, but there was no tenderness. Digital rectal examination revealed an elastic hard on the anterior side of the rectum without palpable intraluminal. Total colonoscopy showed no es or stenosis in the rectum. We evaluated the urinary were due to the compression of the bladder by the tumor. The results of laboratory tests were normal. Serum prostate-specific antigen (PSA) was not available preoperatively. Urinalysis was normal, with no evidence of hematuria. Enhanced CT showed a large retroperitoneal measuring 30 cm in size with multiple septations surrounding the rectum and displacing the bladder, prostate, and seminal vesicle to the right anterior side (Fig. 1). MRI showed a composed of cysts of various sizes ranging from smaller than 1 up to 6 cm and solid components. Whereas most cysts had simple appearance (very high intensity on T2-weighted images), some showed the presence of layering which suggests the likelihood of either fat or blood in content (Fig. 2a, b). Several solid components which showed isointensity on T2-weighted images were enhanced on gadoliniumenhanced fat-saturated T1-weighted images (Fig. 2c f). From these radiological findings, preoperative diagnosis was leiomyoma with cystic degeneration or perivascular epithelioid cell tumor (Fig. 2). Biopsy of the was performed under CT guidance, and histology showed a spindle cell tumor. Immunohistochemically, preoperative biopsy of the tumor showed positive staining for SMA, desmin, and caldesmon while negative for S-100, HMB- 45, and MDM2, indicating smooth muscle differentiation. Differential diagnosis of leiomyoma, low-grade leiomyosarcoma, and perivascular epithelioid cell tumor was made. We suspected the tumor originated from the smooth muscle of the bladder or deep soft tissue in the retroperitoneal space. As the biopsy findings did not reveal obvious evidence of malignancy and because the outer wall of the tumor was relatively smooth, we chose to forego total pelvic exenteration and instead attempt complete macroscopic resection of the tumor with minimal combined resection of adjacent organs. Laparotomy was performed through a midline incision, which revealed a huge from the pelvic floor up to the level of the navel (Fig. 3). During exploration, the bilateral ureter was preserved but the vas deferens was resected. Because the plane of the interface between the bladder and tumor was unrecognizable, we injected air into the bladder and identified the border of the. We dissected the tumor, preserving the bladder and prostate with partial resection of the prostate. The tumor was not attached to the sacrum or levator ani and was mobilized Fig. 1 Enhanced abdominal CT. a, b, c A large multilocular with soft tissue component displacing the bladder (*) and rectum anterolaterally. d The arrow shows the prostate

3 Nakamura et al. World Journal of Surgical Oncology (2019) 17:42 Page 3 of 9 Fig. 2 a, b T2-weighted MRI. Most cysts showed high intensity suggesting simple, and some showed the presence of layering which suggests the likelihood of either fat or blood in content. The arrowheads show the presence of layering within the cystic areas. c, d Non-enhanced fat-saturated T1-weighted MRI and e, f gadolinium-enhanced fat-saturated T1-weighted MRI. Several solid components were enhanced from the pelvic floor. Because the tumor extended into the left pelvic sidewall and surrounded the rectum, we sacrificed the rectum as well as the left hypogastric nerve and left pelvic plexus. Finally, we performed a complete resection of the tumor with low anterior resection. Intraoperatively, the border between the tumor and normal prostate was not so clear. The gross pathologic specimen was a cm solid containing multilocular cavities. Sectioning revealed a multicystic cut surface (Fig. 4), and blackishbrown intratumoral was drained from the tumor. Histologically, the tumor was composed of variously sized dilated glandular structures lined by prostatic epithelia surrounded by fibromuscular stroma (Fig. 5a). Lesions of the well-developed, dilated prostate glands resembling prostatic hyperplasia were also evident (Fig. 5b). The cysts were lined by cuboidal to columnar secretory cells and basally located nuclei (Fig. 5c). Cytologically, we observed no atypical features or mitosis. Epithelial cells of the cysts and stromal glands were positive for PSA on immunohistochemical staining (Fig. 5d). The epithelium cells of the tumor were also positive for AR and NKX3.1 staining, indicating that the tumor originated from the prostate. The spindle cells seen on preoperative biopsy were thought to be stromal components of the tumor. Final histology indicated a giant multilocular prostatic cystadenoma. Postoperatively, whereas the patient developed a pelvic abscess due to urine leakage from the prostatic urethra, he recovered conservatively and was discharged on postoperative day 37. Since there is no positive evidence of adjuvant therapy of this prostatic cystadenoma, the patient is now under follow-up by blood tests and CT scan every 3 6 months.

4 Nakamura et al. World Journal of Surgical Oncology (2019) 17:42 Fig. 3 Intraoperative view. Large with a smooth surface in the lower abdomen and pelvis At 2 months after surgery, the patient had a PSA of ng/ml, which was within the normal ranges. Since then, we have observed no signs of tumor recurrence. The patient was completely asymptomatic at the 6-month follow-up visit and made a full recovery, with no complaints of any urinary disorders or sexual dysfunction. Discussion and conclusions A giant multilocular prostatic cystadenoma is an extremely rare benign neoplasm that originates in the prostate glands. In 1991, Maluf et al. became the first to Fig. 4 Gross photograph. Sectioning revealed a multicystic cut surface Page 4 of 9 describe and designate this rare entity [2]; since then, fewer than 30 cases have been reported (Table 1) [1 21]. This type of tumor is typically located along the midline between the bladder and rectum and identified as a large retroperitoneal. A definitive diagnosis before histological examination of a surgical biopsy is very difficult, but preoperative assessment is important for surgical treatment planning. Previous reports of giant multilocular prostatic cystadenomas indicate that surgical treatment varies from tumor debulking to total pelvic exenteration. The decision concerning surgical margin is influenced by whether or not the is malignant in nature and whether it has invaded adjacent organs. Information on the origin of the is also necessary in order to preserve adjacent organs. Clinical presentation and radiographic features are helpful for preoperative diagnosis. As shown in Table 1, giant multilocular prostatic cystadenoma may occur at any age, with reported patient ages ranging from 23 to 80 years at diagnosis. Presenting are similar to those of benign prostatic hyperplasia and include incomplete voiding and urinary. Almost all cases in the literature noted lower urinary. Enlargement of the also causes abdominal distension and gastrointestinal. Our case initially presented with complaints of abdominal distension, but a detailed interview revealed these to be lower urinary. Urinalysis often reveals hematuria and elevated serum PSA levels. Imaging findings of retroperitoneal tumors are often overlapping, and the first step to understanding the tumors is to divide them into solid or cystic tumors. In addition, their content, precise localization, extent of local invasion, and vascularity may help to define a specific differential diagnosis [22]. CT and MRI scans of the present giant multilocular prostatic cystadenoma revealed a large retroperitoneal solid with multilocular cavities that were compressing adjacent organs, especially the bladder and rectum. As it was located between the bladder and rectum, it was presumed to have arisen from the prostate gland. The comprised cysts of various sizes and soft tissue components. MRI may provide additional information, and T2-weighted imaging of the cysts can be suggestive of either fat or blood in the content. MRI may also show attachment to the prostate. Differential diagnoses of a multicystic retroperitoneal tumor can include liposarcoma, leiomyoma with cystic degeneration, lymphangioma, multilocular peritoneal inclusion cyst, phyllodes variant of atypical prostatic hyperplasia, prostatic abscess, and teratoma. Cysts of the lower male genitourinary tract are uncommon. There are also differential diagnoses for cystic lesions in the pelvis, including Müllerian cysts, utricle cysts, and

5 Nakamura et al. World Journal of Surgical Oncology (2019) 17:42 Page 5 of 9 Fig. 5 Pathological examination of the resected specimen. a Low-power magnification of cystadenoma of the prostate with dense fibromuscular stroma (H&E, original magnification 20). b Cystic dilated glandular structures surrounded by a fibrous stroma resembling prostatic hyperplasia (H&E, original magnification 20). c Glands and cysts are lined by cuboidal to low columnar epithelial cells with basally located nuclei (H&E, original magnification 40). d The epithelium of the cysts stained positively with prostate-specific antigen stain ( 20) seminal vesicle cysts. However, these are typically smaller than the giant multilocular prostatic cystadenoma and not multilocular [23]. Although imaging studies may provide useful information about the extent of the lesion and invasion to adjacent organs, a clear and definitive diagnosis is possible only through histological means. Histologically, a giant multilocular prostatic cystadenoma is composed of multiple cysts in hypocellular fibrous stromal tissue and dense fibrous stroma that corresponds to a focal solid area. It is characterized by cuboidal cells lining the prostate glands and cyst, with positive immunohistochemical staining for PSA in epithelial cells [2]. No previous studies have reported a diagnosis of giant multilocular prostatic cystadenoma preoperatively by biopsy, and biopsy showed benign prostatic glands and stroma in some reports. The biopsy sample of the tumor in our case showed a spindle cell tumor with focal smooth muscle differentiation [2, 24]. If we could diagnose multilocular prostatic cystadenoma before surgery, that is, if we could suspect that the tumor originated from prostate, we might be able to preserve a normal prostate without prostatic urethra injury. Treatment for giant multilocular prostatic cystadenoma is complete surgical excision. However, adherence to surrounding structures often makes complete resection difficult, and clinical suspicion of malignancy may lead to unnecessarily aggressive surgery and no preservation of urogenital or digestive organs. Despite its benign nature, incomplete resection can result in recurrence [2, 12]. To achieve complete resection, we sacrificed the rectum as well as the left hypogastric nerve and left pelvic plexus, but were able to preserve adjacent organs including the prostate, which resulted in no urinary disorders or sexual dysfunction. Complete resection of giant multilocular prostatic cystadenoma should be considered in light of the surgical trauma involved. One recent report found that a gonadotropin-releasing hormone antagonist is effective for recurrent giant multilocular prostatic cystadenoma [12], and this may represent a new treatment option for patients with more aggressive or recurrent giant multilocular prostatic cystadenoma. In conclusion, when a retroperitoneal huge lesion with locular cavities fills the pelvis in men, giant multilocular prostatic cystadenoma should be considered as a differential diagnosis.

6 Nakamura et al. World Journal of Surgical Oncology (2019) 17:42 Page 6 of 9 Table 1 Cases of giant multilocular prostatic cystadenoma Reference Year No. of cases Age (years) Clinical Watanabe et al urinary PSA (ng/ml) Biopsy Radiologic findings 8.2 connective tissue large tumor in the pelvic cavity Size (cm) Volume (g) cloudy similar to semen Contents Treatment Folllow-up Outcome anterior pelvic exenteration 2 years no recurrence Maluf et al Urinary NA Fragments of prostatic tissue NA Brown and others with gray color Surgical excision 4 months No recurrence 38 Increasing abdominal girth, difficulty in micturition NA NA NA Serous, serosanguinous, or mucinous Resection exenteration and pelvic irradiation 2 years No recurrence Lim et al Lower abdominal pain, obstructive voiding NA NA Fluid-filled NA NA En bloc excision NA NA Levy et al Decreased force of urinary stream, hesitancy and frequency of urination NA Negative for malignant cells (cytology) Multi-septated pelvic with thickened irregular walls NA Yellowish-brown Complete surgical excision 8 years No recurrence Morimoto et al Urinary 6 Benign prostatic tissue A with multilocular structure at the position of the prostate Yellow Surgical resection 9 months No recurrence Kirsch et al Hemorrhoidal pain, obstructive voiding, gross hematuria 30.2 No evidence of malignancy (cystic component) Heterogeneous arising from the prostate and extending to the level of the sacral promontory Straw-colored Full enucleation 1 year No recurrence Choi et al Lower abdominal and dysuria NA NA Large multiseptated pelvic with thickened irregular walls Brown, rusty appearing, transparent serous Surgical resection NA NA Seong et al Gross hematuria and frequency 68.2 Chronic inflammatory lesion Oval, lowattenuated between the bladder and rectum, containing cystic and solid portions Reddish-brown serous Excision with bilateral seminal vesicles and vas deferens NA No recurrence

7 Nakamura et al. World Journal of Surgical Oncology (2019) 17:42 Page 7 of 9 Table 1 Cases of giant multilocular prostatic cystadenoma (Continued) Reference Year No. of cases Age (years) Clinical Matsumoto et al Gross hematuria PSA (ng/ml) Biopsy Radiologic findings 14.4 NA (abandoned) Multilocular replacing the prostatic gland Size (cm) Volume (g) Reddish-brown serous Contents Treatment Folllow-up Outcome Radical cystoprostatectomy 24 months No recurrence Rusch et al Urinary, lower urinary tract NA Benign prostatic tissue with cystic dilatation of glands and no evidence of malignancy Multiple septations with some softtissue components 15 NA Hemorrhagic Surgical resection 18 months No recurrence 41 Urinary (recurrence) NA NA Multiseptated cystic 15 NA NA Surgical excision NA NA Datta et al Urinary NA NA Cystic pelvic NA NA Cystoprostatectomy and removal of a portion of the rectum, GnRH antagonist 11 years Recurrence and hormonal therapy Allen et al Lower urinary tract, gross hematuria 3 NA Multiloculated cystic pelvic NA NA Completely removed piecemeal with the largest tissue fragment NA NA Ganesan et al Reduced force of the urinary stream and hesitancy and frequency of urination 1.6 Cystic lesion lined by columnar epithelium with cystic dilatation of prostatic acini Cystic with multiple thin, echogenic internal septations (transabdominal ultrasound) NA Straw-colored Debulking NA NA Tuziak et al Obstructive urinary, urinary 0.04 Fibrous tissue interspersed with prostatic glands having no atypical features Multicystic pelvic 15 NA NA Open prostatectomy without seminal vesicle removal 2 years No recurrence Park et al Abdominal distension, urinary, aspermia 38.2 NA Mass located between the rectum and bladder 9 7 NA NA Mass excision 1 year No recurrence

8 Nakamura et al. World Journal of Surgical Oncology (2019) 17:42 Page 8 of 9 Table 1 Cases of giant multilocular prostatic cystadenoma (Continued) Reference Year No. of cases Age (years) Clinical Chowdhury et al Left loin pain, hematuria, micturition PSA (ng/ml) Biopsy Radiologic findings NA NA Complex septated cystic/soft tissue Lee et al Urinary tract obstruction NA NA Multilocular heterogenous cystic pelvic posterior to the bladder and anterior to the rectum Olgun et al Obstructive voiding symptom, difficulty in defecation 20.2 Only red blood cells and histiocytes with groups of benign epithelial cells Multiseptated, huge cystic lesion that filled the pelvis completely Baad et al Acute urinary, gross hematuria, lower abdominal pain 9.8 Benign prostatic tissue Mutilocular, retrovesicular midline with multiple thin septations Rahman et al Hypogastric pain, constipation, obstructive voiding symptom 20.5 Benign prostatic tissue Multiloculated cystic pelvic, peripheral contrast enhancement Our case Abdominal distension, lower urinary symptom NA Spindle cell tumor with focal smooth muscle differentiation Multiloculated cystic NA not available Size (cm) Volume (g) Contents Treatment Folllow-up Outcome NA NA Debulking NA NA NA Dark brown hemorrhagic Radical cystoprostatectomy 1 year No recurrence solid, cystic component NA Serous and mucinous s Debulking of the 18 months No recurrence NA Straw-colored Partial prostatectomy with enucleation of the NA NA NA Dense brown liquid Laparoscopic 48 months No recurrence Blackish-brown Surgical resection 6 months No recurrence

9 Nakamura et al. World Journal of Surgical Oncology (2019) 17:42 Page 9 of 9 Abbreviations CT: Computed tomography; MRI: Magnetic resonance imaging; PSA: Prostatespecific antigen Acknowledgements The authors thank Tanabe T, Sakamoto R, Moritani K, and Tsukamoto S, all of whom served as staff members at the National Cancer Center Hospital. Funding Not applicable. Availability of data and materials Data supporting the conclusions of this study are included in this published article. Authors contributions YN and DS designed the report, analyzed the data, and wrote the manuscript. YM, YS, SI, and YK collected the patient s clinical data and coordinated and drafted the manuscript. TS and AY performed the pathological diagnosis and wrote part of the manuscript. All authors read and approved the final manuscript. Ethics approval and consent to participate Ethics approval was obtained from our hospital s review board (NCC ). Consent for publication Written informed consent was obtained from the patient. Competing interests The authors declare that they have no competing interests. Publisher s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Author details 1 Department of Colorectal Surgery, National Cancer Center Hospital, Tsukiji, Chuo-ku, Tokyo , Japan. 2 Urology Division, National Cancer Center Hospital, Tokyo , Japan. 3 Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital, Tokyo , Japan. 4 Pathology and Clinical Laboratory Division, National Cancer Center Hospital, Tokyo , Japan. 11. Allen EA, Brinker DA, Coppola D, Diaz JI, Epstein JI. Multilocular prostatic cystadenoma with high-grade prostatic intraepithelial neoplasia. Urology. 2003;61: Datta MW, Hosenpud J, Osipov V, Young RH. Giant multilocular cystadenoma of the prostate responsive to GnRH antagonists. 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